风湿性心脏瓣膜病合并心房颤动患者中DNMT3 A与Kv1.5蛋白的表达变化及相关性研究

目的：探讨风湿性心脏瓣膜病合并心房颤动( AF)患者DNA甲基转移酶3A(DNMT3A)与超速延迟整流性钾通道蛋白(Kv1．5)表达水平变化及其相关性研究。方法将20例风湿性心脏瓣膜病接受瓣膜置换手术患者于体外循环前切取的右心耳组织作为研究对象,根据AF的定义将标本分为AF组(n=10)和窦性心律(SR)组(n=10),分别应用免疫组化、Western blot 法检测心房肌组织中 DNMT3A 和Kv1.5蛋白表达水平变化。结果免疫组化检测显示AF组与SR组相比,DNMT3A蛋白表达增加(P<0．05);而Kv1.5蛋白表达减少(P<0．05)。同时,Western blot检测显示AF组与 SR 组相比,DNMT3A 蛋白表达增加(P <0．05),而Kv1.5蛋白表达减少(P<0．05)。相关性分析显示DNMT3A与Kv1．5之间存在一定负相关性(r =-0．64, P <0．01)。结论 DNMT3A与Kv1.5之间存在负相关性,提示DNMT3A可能参与调控Kv1．5通道蛋白的表达。     

芝麻素通过PI3K/Akt信号通路抑制肥大细胞活化研究

[目的]观察芝麻素对肥大细胞活化的影响并探讨其可能作用机制.[方法]通过IgE介导体外实验观察芝麻素对IgE介导的肥大细胞组织胺的释放及对PI3K/Akt蛋白表达的影响.[结果]与模型对照组比较,芝麻素大、中剂量可明显抑制肥大细胞释放组织胺,且可有效抑制肥大细胞释放炎性细胞因子PI3K/Akt蛋白的表达(P<0.05).[结论]芝麻素抗过敏作用可能部分与抑制PI3K/Akt信号通路有关.     

TAT-GluA2CT interferes with the protective effect of GluA2/TARPγ-8 coupling on nerve injury in status epilepticus model of rats北大核心CSCD

Objective To investigate the protective effect of interfering peptide TAT-GluA2CT on hippocampal neurons in the Lithium chlorine-Pilocarpine status epilepticus model and the optimal time of administration. Methods Male SD rats (72 cases) were induced to status epilepticus by using Lithium chlorine-Pilocarpine, while a control group (n=12) was established.The 72 rats were divided into epilepsy group (n=12), TAT-sham peptide group (n=12), TAT-GluA2CT peptide group (n=48) according to the random number table method, and the TAT-GluA2CT peptide group were further divided into the pre-1 h group (n=12), the post-2 h group (n=12), the post-4 h group(n=12), and the post-6 h group (n=12) according to the administration time of the TAT-GluA2CT peptide. Nissl staining and terminal dUTP nick end labeling (TUNEL) assay were performed on 6 rats each from control group, epilepsy group, TAT-shampeptide group, pre-1 h group, post-2 h group, post-4 h group, and post-6 h group to observe the morphological changes and apoptosis of neurons in the CA1 region of the rat hippocampus.Western blot and co-immunopercipitation test were used to detect the expression of GluA2[second subunit of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) recepter] and the coupling of GluA2/transmembrane AMPA receptor regulatory protein (TARP γ-8) complex in control group, epilepsy group, pre-1 h group, post-2 h group, post-4 h group and post-6 h group.The t-test was used to compare the data differences between 2 groups, and one-way ANOVA was adopted to compare the differences between the groups. Results Compared with the epilepsy group, the number of neurons in each TAT-GluA2CT peptide group increased significantly, and the difference was statistically significant(epilepsy group 20.07±3.51, pre-1 h group 39.40±2.39, post-2 h group 38.43±2.42, post-4 h group 30.30±2.55, and post-6 h group 27.93±3.20, F=235.28, P<0.05). Compared with the epilepsy group, the number of apoptotic cells in each TAT-GluA2CT peptide group was significantly reduced, and the difference was statistically significant(epilepsy group 31.47±3.19, pre-1 h group 7.30±3.45, post-2 h group 9.27±3.81, post-4 h group 12.86±3.08, and post-6 h group 14.43±3.13, F=248.60, P<0.05). Compared with the control group, the expression of hippocampal GluA2 decreased after epilepsy induction, and the difference was statistically significant(control group 21 626.53±2 700.58, epilepsy group 14 578.16±2 917.02, pre-1 h group 13 375.47±3 180.54, post-2 h group 15 244.10±1 390.41, post-4 h group 15 799.16±4 559.49, post-6 h group 15 722.95±1 756.01, F=3.83, P<0.05). No statistical difference was observed in the expression of GluA2 between the TAT-GluA2CT peptide group and the epilepsy group(F=0.45, P=0.77). Compared with the epilepsy group, GluA2/TARPγ-8 complex coupling was decreased in each TAT-GluA2CT peptide group, and the difference was statistically significant(epilepsy group 24 509.80±3 718.54, pre-1 h group 12 055.18±5 847.11, post-2 h group 9 630.51±5 805.17, post-4 h group 12 749.35±7 108.45, post-6 h group 11 092.98±7 330.08, F=10.68, P<0.05). Compared with the epilepsy group, the incubation period of seizures in the pre-1 h group was prolonged and the seizure rating was decreased, with statistically significant differences[epilepsy group (18.58±3.99) min, pre-1 h group (103.25±9.21) min, t=29.23, P<0.05]. Conclusions TAT-GluA2CT peptide can attenuate the neuronal damage in hippocampus of epileptic rats.The neuroprotective effect of TAT-GluA2CT peptide was most obvious at 1 h before or 2 h after administration of Pilocarpine. © 2022 Chin J Pathol, June. All rights reserved.     

α-Sarcoglycanopathy的临床和病理学特征(附2例报告)

目的探讨α-Sarcoglycanopathy的临床和病理学特征。方法回顾性分析2例α-Sarcoglycanopathy患者的临床资料。结果本组2例患者均表现为近端肌肉无力,进行性加重。肌肉活检均可见肌间结缔组织及脂肪组织增生,肌纤维萎缩,偶见肌纤维变性、坏死和吞噬现象,未见炎细胞浸润;免疫组化染色示抗α-Sarcoglycan蛋白完全缺失,抗β、γ、δ-sacogiycan蛋白和抗dystrophin蛋白部分缺失。结论α-Sarcoglycanopathy临床表现较其他类型肌营养不良无特异性,病理学特征为免疫组化染色示抗α-Sarcoglycan蛋白完全缺失。     

糖原合成激酶-3(GSK-3)与抑郁症的研究进展

对糖原合成激酶-3(GSK-3)与抑郁症关系的研究进行综述。     

阿托伐他汀联合尿激酶溶栓治疗对大脑中动脉梗死大鼠caspase-3表达的影响

目的观察阿托伐他汀联合尿激酶溶栓治疗对大脑中动脉梗死(MCAO)大鼠脑组织caspase-3表达的影响。方法采用血栓栓塞法制备SD大鼠大脑中动脉急性脑梗死模型,随机分为阿托伐他汀组、尿激酶组、联合治疗组和对照组。缺血3 h给予阿托伐他汀或相同体积生理盐水,缺血4 h给予尿激酶或相同体积生理盐水治疗。治疗前3h和缺血24h行神经功能缺损评分,缺血24h取脑,采用氯化三苯四唑(TTC)染色法观察脑梗死体积,免疫组织化学法检测大鼠脑组织caspase-3的表达。结果与对照组比较,阿托伐他汀组、尿激酶组和联合治疗组大鼠缺血24 h神经功能缺损评分明显降低(P<0.05),梗死体积明显缩小(P<0.05)。与阿托伐他汀组比较,尿激酶组和联合治疗组神经功能改善程度及梗死体积减小程度更显著(P<0.05)。各组大鼠均未发现脑出血。与对照组相比,阿托伐他汀组和联合治疗组caspase-3表达显著减少(P<0.05)。与阿托伐他汀组比较,联合治疗组caspase-3减少更为明显(P<0.05)。与对照组相比,尿激酶组caspase-3表达无统计学差异(P>0.05)。结论阿托伐他汀联合尿激酶溶栓治疗脑梗死能更大程度降低caspase-3的表达,有提高疗效的趋势。     

遗传性脊髓小脑共济失调3型MRI检查的应用及进展

脊髓小脑性共济失调(spinocerebellar ataxia,SCA)是一组以迟发、进展性小脑及其传入和传出连接功能退化为特点的遗传性神经系统变性疾病,该病根据基因、染色体位点及生化产物可分为SCA 1-SCA 29等约30种,中国发病率最高的亚型为脊髓小脑性共济失调3型(spinocerebellar ataxia type 3,SCA3),其具有渐进性、隐匿性、遗传早现等疾病特点,但早期临床症状、体征不典型,该病临床体征与多发性硬化、多系统萎缩等疾病存在重叠性,难以通过临床体征来确诊SCA3。早期确诊SCA3并尽早针对性治疗有重要意义。近年来,MRI在SCA3的诊断、鉴别诊断、病情变化与神经系统结构异常病变的位置相关性方面有进一步的研究及发现,其中常规MRI扫描主要提供基础解剖结构成像及功能影像学成像基础信息,基于体素形态学分析(VBM)、扩散张量成像(DTI)、磁共振波谱成像(MRS)则对病变中脑实质代谢、微结构、血流灌注等变化有着较高的敏感性,本文对多种影像学技术在SCA3中的应用进行综述。     

关节挛缩伴强直脊柱综合征1例报道并文献复习

目的报道1例以关节挛缩伴强直脊柱综合征为主要表现的肢带型肌营养不良2A(LGMD2A)病例,提高对以关节挛缩及强直脊柱综合征为主要表型的肌肉疾病的认识。方法收集1例以关节挛缩伴强直脊柱综合征为表征最终确诊为LGMD2A患者的临床资料、肌肉活检(病理染色、Western blot)、基因检测和肌肉影像学等资料,结合文献复习进行分析。结果患者除早期出现的全身关节挛缩伴强直脊柱外,合并有四肢近端肌肉萎缩、无力,明显翼状肩。家族史提示常染色体隐性或X连锁隐性遗传可能;肌肉MRI示大腿后群、内侧群,小腿后群显著受累;肌肉病理检查示肌营养不良表现;Western blot检测示calpain-3条带完全缺失,CAPN3基因检测示患者携带c.534AG(I178M)及c.411dupC(C137fs)双杂合突变,并均为新发突变。最终诊断为LGMD2A。结论临床中对于早发关节挛缩伴强直脊柱综合征的患者,需考虑LGMD2A可能,肌肉MRI可为LGMD2A的诊断和鉴别诊断提供重要线索。     

3-羟基丁酸尿症伴小脑性共济失调病例报告

目的报告3-羟基丁酸尿症伴小脑性共济失调的病例。方法收集以共济失调为首发症状的3-羟基丁酸尿症患者的临床资料,结合文献复习进行分析。结果 3-羟基丁酸尿症患者经临床体检发现有小脑共济失调的体征和尿中3-羟基丁酸、乙酰乙酸、2-酮-3-甲基戊酸、2-酮-异己酸显著升高。结论发现1例3-羟基丁酸尿症伴小脑性共济失调病例。     

颅脑损伤大鼠皮质HIF-1α和GLUT-3的表达及意义

目的探讨颅脑损伤(traumatic brain injury,TBI)大鼠皮质脑组织缺氧诱导因子-1α(HIF-1α)和葡萄糖转运蛋白-3(GLUT-3)的表达变化,并进行相关性研究。方法 108只SD大鼠随机分为正常对照组(n=12)和实验组(n=96)。实验组采用自由落体打击法建立大鼠颅脑损伤模型,正常对照组不做处理。分别采用RT-PCR及免疫组化检测伤后1、4、8、12 h及1、3、7、14 d挫伤灶周围HIF-1α和GLUT-3 m RNA及蛋白的表达。结果 RT-PCR结果显示:实验组HIF-1α和GLUT-3 m RNA在伤后4 h升高,12 h达高峰,7 d基本正常;伤后4 h~3 d与正常对照组比较,差异均有统计学意义(P0.05)。Western blot检测显示:实验组HIF-1α和GLUT-3蛋白在伤后4 h表达升高,1 d达高峰,7 d降至正常水平;伤后4 h~3 d与正常对照组差异均有统计学意义(P0.05)。相关性分析表明:HIF-1α与GLUT-3在m RNA及蛋白水平均呈正相关(r=0.894,P0.05;r=0.921,P0.05)。结论 TBI后脑组织HIF-1αm RNA及蛋白的表达上调,可能介导GLUT-3的表达增加,从而发挥神经保护作用。